PROJECT SUMMARY/ABSTRACT: HIV viral load (VL) monitoring is a crucial component of the ongoing scale-up of antiretroviral therapy (ART) in Sub-Saharan Africa. Uganda recently launched a nationwide VL testing system; however, significant implementation gaps have emerged in three critical areas: (1) inadequate VL ordering, (2) slow generation and reporting of VL results, and (3) suboptimal interpretation of VL results for adherence counseling. Additionally, significant disparities exist in sub-populations at high-risk of virologic failure including (1) pregnant women, (2) children and adolescents, (3) persons whose last VL was detectable, and (4) persons missing a VL test. To address the implementation gaps on how best to improve VL ordering, speed up VL turnaround time, and improve VL counseling, we propose a comparative effectiveness, clinic-level cluster randomized trial of a targeted, multi-component intervention package called ?RAPID-VL? among 1,200 high-risk and non-high-risk patients in 20 PEPFAR-supported ART clinics in southwest Uganda. Anchored in the PRECEDE implementation science framework, ?RAPID-VL? consists of (1) a VL ordering flowsheet to increase correct VL ordering, coupled with a performance feedback system to reinforce best practices, (2) a point-of-care VL machine at a hub near the clinics that will speed up the generation and delivery of VL results to clinicians, and (3) a VL counseling package that teaches clinicians an efficient method for counseling patients on VL results. Aim 1: Determine the comparative effectiveness of the RAPID-VL intervention on VL ordering and VL turnaround time: We will randomize HIV clinics to RAPID-VL vs. standard VL procedures (n=10 clinics each, 60 patients/clinic, comprised of 20 non-high risk patients plus 10 high risk patients in each of 4 categories), and will compare (1) guideline-indicated VL ordering, (2) VL turnaround time, (3) VL suppression, (4) VL re- suppression after a detectable result, and (5) switching to 2nd line ART. Aim 2: Identify facilitators and barriers to implementation, as well as perceived utility of RAPID-VL from both patient and clinician perspectives. We will measure fidelity to each RAPID-VL component via in-clinic observations and training assessments. We will perform qualitative interviews of 20 clinicians and 40 patients to capture facilitators, barriers, acceptability and sustainability of RAPID-VL and examine its perceived utility.Aim 3: Determine the costs, cost-effectiveness, and incremental gain costs of RAPID-VL: We will conduct micro-costing analyses of key cost inputs including training, clinician effort, point-of-care VL machinery, and transportation costs. We will compare these to costs of the current standard of care DBS-based system on unit cost and ?cost-per-added success.? We will also estimate cost per disability-adjusted life year (DALY) averted for RAPID-VL. Our overall objective is to rigorously test a novel intervention to improve VL operations in PEPFAR- supported Ugandan HIV clinics. Our long-term goal is to maximize the public health impact of ART by optimizing processes for VL testing. This will improve health, lower mortality, and accelerate ART expansion.